Nintedanib in children and adolescents with fibrosing interstitial lung diseases

Background Childhood interstitial lung disease (ILD) comprises a spectrum of rare ILDs affecting infants, children and adolescents. Nintedanib is a licensed treatment for pulmonary fibrosis in adults. The primary objectives of the InPedILD trial were to determine the dose-exposure and safety of nintedanib in children and adolescents with fibrosing ILD.Methods Patients aged 6-17 years with fibrosing ILD on high-resolution computed tomography and clinically significant disease were randomised 2:1 to receive nintedanib or placebo for 24 weeks and then open-label nintedanib. Dosing was based on weight-dependent allometric scaling. Co-primary end-points were the area under the plasma concentration-time curve at steady state (AUC Tau,ss) at weeks 2 and 26 and the proportion of patients with treatment-emergent adverse events at week 24.Results 26 patients received nintedanib and 13 patients received placebo. The geometric mean (geometric coefficient of variation) AUC Tau,ss for nintedanib was 175 mu gmiddothmiddotL-1 (85.1%) in patients aged 6-11 years and 160 mu gmiddothmiddotL-1 (82.7%) in patients aged 12-17 years. In the double-blind period, adverse events were reported in 84.6% of patients in each treatment group. Two patients discontinued nintedanib due to adverse events. Diarrhoea was reported in 38.5% and 15.4% of the nintedanib and placebo groups, respectively. Adjusted mean +/- SE changes in percentage predicted forced vital capacity at week 24 were 0.3 +/- 1.3% in the nintedanib group and-0.9 +/- 1.8% in the placebo group.Conclusions In children and adolescents with fibrosing ILD, a weight-based dosing regimen resulted in exposure to nintedanib similar to adults and an acceptable safety profile. These data provide a scientific basis for the use of nintedanib in this patient population.